A Phase-2 Exploratory Randomized Controlled Trial of INOpulse in Patients with Fibrotic Interstitial Lung Disease Requiring Oxygen.

Rationale: Patients with fibrotic interstitial lung disease often progress to the point of requiring supplemental oxygen. This is invariably accompanied by an impaired quality of life and limitations on activities of daily living. Objectives: This study aimed to assess the improvement in physical activity in patients with interstitial lung disease requiring supplemental oxygen treated with pulsed inhaled nitric oxide via INOpulse (Bellerophon Therapeutics). In addition, it sought to explore the safety and clinical benefits of INOpulse on multiple patient-reported outcomes. Methods: Ambulatory patients with fibrotic lung disease on supplemental oxygen were randomized in a 2:1 ratio to inhaled nitric oxide at 45 µg/kg ideal body weight/h (iNO45) or placebo for 4 months (3 months after baseline) of blinded treatment. The study assessed multiple exploratory efficacy endpoints, including moderate to vigorous physical activity as measured by actigraphy and patient-reported outcomes using the University of California San Diego shortness of breath questionnaire and the St. George's Respiratory Questionnaire (SGRQ). Results: A total of 44 patients (30 iNO45 and 14 placebo) were enrolled. A placebo-corrected clinical benefit of 12.3 min/d increase in MVPA was observed in the iNO45 group. Clinically meaningful beneficial trends were observed for the University of California San Diego shortness of breath questionnaire (6.05 points) and the SGRQ total (3.75) scores, as well as the SGRQ activity (5.84), and SGRQ impact (6.30) domains. Conclusions: INOpulse was well tolerated and associated with maintenance of physical activity and improved symptomatology in patients with interstitial lung disease who require supplemental oxygen. Further validation of this beneficial effect warrants further study in a phase-3 trial that is currently underway.

STEMI associated with SARS-CoV-2 infection and the use of ECMO as a potential therapeutic approach in addition to the PCI.

A 55-year-old male presented to the emergency department with the complaints of chest pain that started 4 h before presentation. Pain was located over the anterior chest, 5 out of 10 intensity, with radiation to the left arm. Chest x-ray on admission showed severe diffuse bilateral pulmonary infiltrates concerning for COVID-19 pneumonia. Electrocardiogram showed inferior and lateral ST-segment elevation compatible with acute inferolateral myocardial infarction. Successful percutaneous coronary intervention (PCI) of the proximal and mid-right coronary artery using the balloon angioplasty and drug-eluting stent was performed. Post-PCI stenosis was 0% with a thrombolysis in myocardial infarction (TIMI) flow of 3. Five-day course of azithromycin and hydroxychloroquine was completed with no improvement overall. Patient received two doses of 400 mg of tocilizumab intravenously on hospital days 5 (HD#5) and #6. The patient was proned, on FiO2 100%, PEEP 15 cm H2O, on epoprostenol sodium and paralytics and eventually received venovenous ECMO, which improved outcome.

Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension.

OBJECTIVES: The aim of this study was to evaluate the relationships between echocardiographic findings and clinical outcomes in patients with severe primary pulmonary hypertension (PPH). BACKGROUND: Primary pulmonary hypertension is associated with abnormalities of right heart structure and function that contribute to the poor prognosis of the disease. Echocardiographic abnormalities associated with PPH have been described, but the prognostic significance of these findings remains poorly characterized. METHODS: Echocardiographic studies, invasive hemodynamic measurements and 6-min walk tests were performed and outcomes prospectively followed in 81 patients with severe PPH. Subjects were participants in a 12-week randomized trial examining the effects of prostacyclin plus conventional therapy compared with conventional therapy alone. RESULTS: During the mean follow-up period of 36.9 +/- 15.4 months, 20 patients died and 21 patients underwent transplantation. Pericardial effusion (p = 0.003) and indexed right atrial area (p = 0.005) were predictors of mortality. Pericardial effusion (p = 0.017), indexed right atrial area (p = 0.012) and the degree of septal shift in diastole (p = 0.004) were predictors of a composite end point of death or transplantation. In multivariable analyses incorporating clinical, hemodynamic and echocardiographic variables, pericardial effusion and an enlarged right atrium remained predictors of adverse outcomes. Six-minute walk results, mixed venous oxygen saturation and initial treatment randomization were also independently associated with a poor prognosis. CONCLUSIONS: Pericardial effusion, right atrial enlargement and septal displacement are echocardiographic abnormalities that reflect the severity of right heart failure and predict adverse outcomes in patients with severe PPH. These characteristics may help identify patients appropriate for more intensive medical therapy or earlier transplantation.